We have many factors to consider when making a dissolution method. What apparatus, speed, filter choice, etc. Of these factors, the one I get the most questions about is media selection – especially surfactants in media selection. So, what is a surfactant and why do we use them? What do we need to consider when working with them?
First, what is a surfactant? Surfactants are chemicals which reduce surface tension, and in sufficient concentration can increase the solubility of our media. Outside of dissolution, our experience with surfactants are soaps like laundry detergents. In cleaning, surfactants work on the surface of the stain, etc. and then aid in solubilizing it. In dissolution, surfactants act on the surface of our formulation and potentially increase the solubility of our drug in the media.
When used at low concentrations, surfactants are a wetting agent – helping the media interact with our formulation’s surface. At higher concentrations, they also improve solubility. The level at which surfactants begin to improve solubility is referred to as the critical micelle concentration (CMC). The CMC will vary depending on the media pH, temperature, and other factors. When designing a dissolution method, we just want to avoid a concentration very close to that CMC as it could lead to higher variability – basically operating at a pivot point isn’t desirable for this purpose.
If you need surfactants to aid in solubility, you should only use as much as needed to allow for your product to meet sink condition in the media. Sink condition is the ability of your dissolution media to dissolve 3x the amount of drug that is in your dosage form. If you use too much surfactant, you risk losing the ability of your dissolution method to discriminate. You should evaluate different surfactant types as well to see what works best for your product. Surfactants can be anionic, cationic, or non-polar – and it’s good to consider one of each of these in development. SLS, Tween, and CTAB are some good choices to consider.
Surfactants aren’t without other challenges you should consider. They cause foaming which may need to be dealt with in autosamplers. SLS can denature enzymes used for cross-linking. Foaming can impact volume accuracy. Foaming can even cause overflowing in Apparatus 3 (Bio-Dis). These all can be dealt with – and might be subjects for some other posts here.
Related:
Resource Person: Ken Boda (Dissolution Product Specialist at Agilent Technologies)